A moderate low-carbohydrate diet has been receiving attention in the dietary management of type 2 diabetes (T2DM). A fundamental issue has still to be addressed; how much carbohydrate delta-reduction (?carbohydrate) from baseline would be necessary to achieve a certain decrease in hemoglobin A1c (HbA1c) levels.

Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction and dementia in the elderly. T2DM has been thought to be associated with vascular diseases, eventually leading to vascular dementia, but recent studies have established that T2DM is also associated with Alzheimer's disease (AD). With the increase in the number of elderly individuals with T2DM, the number of diabetic patients with cognitive dysfunction has been increasing. T2DM may accelerate AD-associated pathologies through insulin resistance. Vascular pathologies may also be associated with cognitive dysfunction and dementia in T2DM subjects. Several other mechanisms also seem to be involved in T2DM-related cognitive dysfunction. More investigations to clarify the association of T2DM with cognitive impairment are warranted. These investigations may help to increase our understanding of AD and open a new door to the development of therapeutics. Recent pharmaceutical advancement in T2DM treatment has resulted in the availability of a wide range of antidiabetics. Some evidence has suggested that antidiabetic therapies help to prevent cognitive dysfunction. At present, however, the optimal level of blood glucose control and the best combination of medications to achieve it in terms of cognitive preservation have not been established. More investigation is warranted. Cognitive dysfunction is an emerging new complication of T2DM that requires further study.

We surveyed the care burden of family caregivers, their satisfaction with the services, and whether their care burden was reduced by the introduction of the LTCI care services. We randomly enrolled 3000 of 43,250 residents of Nagoya City aged 65 and over who had been certified as requiring long-term care and who used at least one type of service provided by the public LTCI; 1835 (61.2%) subjects returned the survey. A total of 1015 subjects for whom complete sets of data were available were employed for statistical analysis. Analysis of variance for the continuous variables and ?(2) analysis for that categorical variance were performed. Multiple logistic analysis was performed with the factors with p values of <0.2 in the ?(2) analysis of burden reduction. A total of 68.8% of the caregivers indicated that the care burden was reduced by the introduction of the LTCI care services, and 86.8% of the caregivers were satisfied with the LTCI care services. A lower age of caregivers, a more advanced need classification level, and more satisfaction with the services were independently associated with a reduction of the care burden. In Japanese LTCI, the overall satisfaction of the caregivers appears to be relatively high and is associated with the reduction of the care burden.

Donepezil, a cholinesterase inhibitor (ChEI) that is widely used to treat Alzheimers disease, is thought to act by increasing extracellular acethylcholine (ACh) in the central nervous system. The effects of the administration of ChEIs on the autonomic nervous system, however, are complex and controversial.

We previously demonstrated that the direct microinjection of cholinesterase inhibitor (neostigmine) into the hippocampus in rats activated the hypothalamo-pituitary -adrenal axis and increased the level of norepinephrine in the plasma. In the current study we tried to measure the effects of neostigmine injection into the hippocampus using the non-invasive measure of heart rate variability (HRV).

In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients.

The number of elderly with cognitive dysfunction has been increasing in developed countries. Several studies have shown that diabetes is a risk factor for declines in cognitive function and, recently, numerous studies have demonstrated that exercise improves insulin resistance (IR). However, no studies have been undertaken to examine the relationship between IR and cognitive dysfunction.

Although recent evidence has indicated that type 2 diabetes mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or dementia, few studies have prospectively observed this potential cognitive decline. In the current study, we performed cognitive assessments at baseline and after 3 years in the same patient group in an attempt to reveal the contributions of diabetes-related factors to the increased decline in cognitive function in elderly patients with T2DM.

Despite the high prevalence of anemia and depression in the elderly, there have been few studies exploring the association between these two conditions. In the current study, we analyzed the association of hemoglobin level and depressive mood in a group of community-dwelling elderly at high risk of requiring care.

Aging is a result of damage accumulation, and understanding of the mechanisms of aging requires exploration of the cellular and molecular systems functioning to control damage. Senescence-accelerated mouse prone 10 (SAMP10) has been established as an inbred strain exhibiting accelerated aging with an earlier onset of cognitive impairment due to neurodegeneration than the senescence-resistant control (SAMR1) strain. We hypothesized that tissue-protective responses of glial cells are impaired in SAMP10 mice. We injected kainic acid (KA) to induce hippocampal injury and studied how cytokines were upregulated on Day 3 using 3-month-old SAMP10 and SAMR1 mice. Following microarray-based screening for upregulated genes, we performed real-time RT-PCR and immunohistochemistry. Results indicated well-orchestrated cytokine-mediated glial interactions in the injured hippocampus of SAMR1 mice, in which microglia-derived interferon (IFN)-? stimulated astrocytes via IFN-? receptor and thereby induced expression of CXCL10 and macrophage inflammatory protein (MIP)-1?, and activated microglia produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and osteopontin (OPN). OPN was the most strongly upregulated cytokine. CD44, an OPN receptor, was also strongly upregulated in the neuropil, especially on neurons and astrocytes. KA-induced hippocampal upregulation of these cytokines was strikingly reduced in SAMP10 mice compared to SAMR1 mice. On Day 30 after KA injection, SAMP10 but not SAMR1 mice exhibited hippocampal layer atrophy. Since the OPN-CD44 system is essential for neuroprotection and remodeling, these findings highlight the defects of SAMP10 mice in cytokine-mediated neuroprotective glia-neuron interactions, which may be associated with the mechanism underlying the vulnerability of SAMP10 mice to age-related neurodegeneration.

Previous studies have shown that the verbal fluency test (VFT) is a sensitive measure of cognitive dysfunction in Alzheimers disease (AD). However, other studies have shown that the performances were significantly influenced by education in the normal elderly population. In order to examine the utility of the VFT as a tool for screening for AD, it is necessary to study the effect of education not only in the cognitively intact population but also in the population of early AD patients.

With an aim to improve quality of life in caregivers of dementia patients, we examined the effect of regular exercise on caregivers sense of burden and their physical symptoms. Participants were 31 elderly caregivers living with older patients diagnosed with Alzheimers-type dementia. They were randomly assigned to either the intervention group, who were prescribed regular exercise with moderate-intensity: 3 metabolic equivalents (3METs), 3 times per week for 12 weeks, or the control group, who did not receive any prescription. In the intervention group, significant reductions in the Zarit caregiver burden interview (ZBI) score and in the frequency of feeling fatigued, and an improvement in quality of sleep were observed at follow-up (p < 0.05), while no such changes were observed in the control group. These results suggest that obtaining sustainable habit of moderate exercise may improve quality of life in caregivers of demented patients.

Physical activity in the elderly has a significant influence on their health status. Studies have shown that elderly caregivers have fewer physical activities relative to non-caregivers. The present study aimed to identify factors associated with lower physical activity in elderly caregivers of demented patients. A cross-sectional survey of 50 elderly caregivers living with patients diagnosed with Alzheimers-type dementia showed that the Zarit caregiver burden interview (ZBI) scores were significant predictors of physical activity measured by the questionnaire score (QS) of physical activities. Among the three subscales of the QS, it was only leisure time activity scores (LS) that the ZBI scores significantly predicted. The numbers of chronic diseases were associated with lower household activity scores (HS) and sport activities scores (SS). Physical activities, in particular leisure activities, were found to be inversely associated with care burden assessed by the ZBI. Interventions to increase the physical activity levels of older caregivers may improve their health status and quality of life.

The rates of co-morbid depression with elderly diabetes are reportedly high. Although the intake of several nutrients has been suggested to be associated with depressive symptoms, the chronic effects of carbohydrate intake on mood remain unclear. In the current study, the association of the carbohydrate energy/total energy (C/E ratio) and other factors with depressive mood in the diabetic elderly were investigated.

Recent studies have revealed that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia, especially those related to Alzheimers disease (AD). Basic research suggests that insulin accelerates Alzheimer-related pathology through its effects on the amyloid beta (Abeta). Several pathological studies with autopsy samples have demonstrated, however, that dementia subjects with diabetes have less AD-related neuropathology than subjects without diabetes. We and others have reported that small vessel diseases affect cognitive function in older diabetics. Asymptomatic ischemic lesions in T2DM subjects may lower the threshold for the development of dementia and this may explain the inconsistency between the basic research and clinicopathological studies. Longitudinal follow-up of T2DM subjects without overt dementia using both amyloid imaging and magnetic resonance imaging may elucidate these issues. Following up until the development of overt dementia would make it possible to compare both amyloid load and ischemic lesions before and after the development of dementia. Moreover, amyloid imaging in non-demented older people with or without insulin resistance would verify the role of insulin in the processing and deposition of Abeta. Vascular risk factors may represent a therapeutic target, while neurodegenerative pathologies have not yet been amenable to treatment. It remains to be investigated whether medical interventions on vascular risk factors have protective effects against the development and progress of dementia.

Acute gastrointestinal events (mostly manifested by nausea, vomiting, or loss of appetite) are class effects of all cholinesterase inhibitors, which are prescribed for the treatment of Alzheimers disease. The underlying mechanism, however, has been unclear. Because corticotropin-releasing hormone is related to appetite control, we focused on the activation of the hypothalamo-pituitary-adrenal system and food intake following the administration of the cholinesterase inhibitor, donepezil, in rats. We monitored the plasma concentrations of adrenocorticotropic hormone, c-Fos, in the paraventricular nucleus, and intakes of rat chow for 3 h after the first administration of donepezil, and 2 weeks later, after daily administration of donepezil. The intragastric administration of 3 mg/kg of donepezil significantly increased the plasma adrenocorticotropic hormone levels and c-Fos expression in the paraventricular nucleus, and decreased the food intake on the first day. The increase in adrenocorticotropic hormone and loss of appetite after oral administration of the drug were attenuated after daily administration for 2 weeks.

A low-carbohydrate diet (LCD) achieves good glycemic control in type 2 diabetes (T2DM) compared with a high-carbohydrate diet. With respect to energy metabolism, acute metabolic responses to high-carbohydrate meals (HCMs) have not been determined in LCD patients with T2DM.

In our previous study, a lesion in the lateral bed nucleus of the stria terminalis (BNSTL) was found to significantly attenuate the elevation of adrenocorticotropic hormone (ACTH) in plasma during microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus. The current study was designed to examine the role of the BNSTL in regulation of blood glucose elevation induced by hippocampal neostigmine injection.

We previously demonstrated that a loosely restricted 45%-carbohydrate diet led to greater reduction in hemoglobin A1c (HbA1c) compared to high-carbohydrate diets in outpatients with mild type 2 diabetes (mean HbA1c level: 7.4%) over 2 years. To determine whether good glycemic control can be achieved with a 30%-carbohydrate diet in severe type 2 diabetes, 33 outpatients (15 males, 18 females, mean age: 59 yrs) with HbA1c levels of 9.0% or above were instructed to follow a low-carbohydrate diet (1852 kcal; %CHO:fat:protein = 30:44:20) for 6 months in an outpatient clinic and were followed to assess their HbA1c levels, body mass index and doses of antidiabetic drugs. HbA1c levels decreased sharply from a baseline of 10.9 ± 1.6% to 7.8 ± 1.5% at 3 months and to 7.4 ± 1.4% at 6 months. Body mass index decreased slightly from baseline (23.8 ± 3.3) to 6 months (23.5 ± 3.4). Only two patients dropped out. No adverse effects were observed except for mild constipation. The number of patients on sulfonylureas decreased from 7 at baseline to 2 at 6 months. No patient required inpatient care or insulin therapy. In summary, the 30%-carbohydrate diet over 6 months led to a remarkable reduction in HbA1c levels, even among outpatients with severe type 2 diabetes, without any insulin therapy, hospital care or increase in sulfonylureas. The effectiveness of the diet may be comparable to that of insulin therapy.

Management of metabolic syndrome (MetS) seems to constitute an efficient strategy to attain successful ageing. Although the clinical entity of MetS in patients with diabetes mellitus has been discussed, there is very little information on MetS-type cardiometabolic risk factor clustering in diabetic elderly.

Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive decline. However, the etiology of dementia and cognitive impairment in people with T2DM is probably multifactorial, and the precise underlying mechanism remains unclear. Good metabolic control in elderly subjects with T2DM may contribute to prevention of the development and/or progression of cognitive decline in elderly diabetic subjects, but hypoglycemia must be avoided. Appropriate well-balanced glycaemic control should be provided to diabetic subjects with cognitive impairment. Demented diabetic patients tend to lose self-caring ability, and behavioural and psychological symptoms of dementia (BPSD) and depressive mood; the symptoms often associated with dementia, make the management of diabetes complicated and difficult. Considering the progressive aging world-wide, more research to investigate the association between T2DM and dementia process, as well as the best way to manage this population, will be important.

Methods of assessing driving abilities in the elderly are urgently needed. Although the driving simulator (DS) appears to be a safe and cost-effective method of objectively evaluating driving performance, it may pose adaptation problems for elderly adults. In this study, we examined age-related adaptation deficits on the DS.

Donepezil is widely used to delay the progression of cognitive dysfunction in patients with Alzheimers disease (AD), but the efficacy of pharmacotherapy is often reduced by poor adherence to medication. In order to improve adherence by providing information about AD and the significance of pharmacotherapy, the Donepezil Outpatient Consultation Service (DOCS) was set up. The influence of this service on medication persistence was assessed in the present study.

Urinary albumin excretion (UAE) is a marker of the early phase of diabetic nephropathy. Although a low-carbohydrate diet (LCD) has been shown to effectively improve glycemic control in patients with type 2 diabetes (T2DM), its effects on UAE remain unknown.

The incidence of type 2 diabetes mellitus (T2DM) has risen, and this trend is likely to continue. Recent advances suggest that T2DM is a risk factor for cognitive decline. We are now encountering novel complications of T2DM, namely cognitive dysfunction and dementia. Although the treatment strategy for diabetic patients with neurocognitive dysfunction has received a great deal of attention, the appropriate level of glycemic control for the prevention of the development and/or progression of cognitive decline in elderly diabetic patients remains to be elucidated. Another issue in diabetic treatment in patients with cognitive dysfunction is the selection of medicines. The best choice and combination of antidiabetic medications for the preservation of cognition should also be studied. Ample studies suggest that exercise helps to preserve cognitive function, although existing evidence does not necessarily indicate its effectiveness exclusively in diabetic patients. Exercise is a helpful non-pharmacological therapy. Considering the progressive aging of the worldwide population, more research to investigate the best way to manage this population is important.

Functional status of those who have very mild cognitive impairment have not been sufficiently investigated. In the current study, we analyzed the characteristics of functional awareness in older adults who had cognitive impairment and were at high risk of requiring support/care (termed as specified elderly at high risk for care needs in the long-term care insurance scheme).

Diabetic nephropathy is a serious complication in patients with type 2 diabetes. The aim of this study was to explore the factors associated with the progression of this complication in elderly patients with type 2 diabetes.

Considerable attention has been paid to the association between type 2 diabetes mellitus (T2DM) and cognitive dysfunction in the elderly. T2DM is often comorbid with several other metabolic disturbances, including hypertension and dyslipidemia. These comorbid diseases might be associated with cognitive impairment. Many clinical indices should be included as variables for the association with cognitive decline. In the current study, we tried to identify the associated factors with cognitive decline during a 6-year period in elderly T2DM considering the changes in the clinical indices during the follow-up period.

Recent evidence has shown that type 2 diabetes mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or dementia. However, the precise mechanisms have not yet been elucidated. In the current study, we attempted to elucidate the association of clinical indices and diabetic complications at baseline with cognitive declines after 6-year follow up in type 2 diabetic elderly.

To assess the preventive effect of atorvastatin on cardiovascular disease and on diabetes-related events in elderly type 2 diabetic patients enrolled in the Japanese Elderly Diabetes Intervention Trial (J-EDIT).

It is well known that a decline in physical activity is associated with lifestyle-related diseases including cardiovascular (CV) events. However, little is known about the association between physical activity and CV events in elderly patients, because recent accumulating reports have mainly dealt with middle-aged populations. In this study, we investigated the correlation between physical activity and CV events in Japanese elderly patients with type 2 diabetes mellitus (T2DM).

A decline in physical activity has been shown to be associated with metabolic syndrome (MetS), leading to cardiovascular events. However, this is difficult to manage well in the elderly with multiple atherosclerotic risk factors. In this study, we investigated the correlation between physical activity and clinical parameters in the presence and absence of MetS in Japanese elderly subjects with type 2 diabetes mellitus (T2DM). In addition, we determined which factor, calorie intake or physical activity, mainly contributes to the prevalence of MetS.

Many reports have shown that vegetable intake is effective in inhibiting the onset and progression of diabetes mellitus, although the amount of vegetable intake required to be effective remains as unclear. The present study therefore aimed to clarify the relationship between the amount of vegetable intake and glycated hemoglobin A1c (HbA1c) and other metabolic parameters using male Japanese type 2 diabetic patients aged 65 years or older as subjects.

In diet therapy for diabetes, optimal energy intake and the energy distribution of macronutrients (protein : fat : carbohydrate [PFC] energy ratio) are important. We aimed to clarify the correlation between the PFC energy ratio and metabolic parameters including glycated hemoglobin A1c (HbA1c) and triglycerides in Japanese elderly patients with type 2 diabetes mellitus aged 65 years or older.

To determine the status of nutritional intake in elderly Japanese patients with type 2 diabetes aged 65 years or older, and to clarify relations of nutritional intake to age, sex and body mass index (BMI).

To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients.

Diabetes mellitus is recognized as a group of heterogeneous disorders with the common elements of hyperglycaemia and glucose intolerance due to insulin deficiency, impaired effectiveness of insulin action, or both. The prevalence of Type 2 diabetes mellitus (T2DM) increases with age and dementia also increases its incidence in later life. Recent studies have revealed that T2DM is a risk factor for cognitive dysfunction or dementia, especially those related to Alzheimers disease (AD). Insulin resistance, which is often associated with T2DM, may induce a deficiency of insulin effects in the central nervous system (CNS). Insulin may have a neuroprotective role and may have some impact on acetylcholine (ACh) synthesis. Hyperinsulinemia, induced by insulin resistance occurring in T2DM, may be associated with insulin deficiency caused by reduced insulin transport via the blood brain barrier (BBB). Insulin has multiple important functions in the brain. Some basic research, however, suggests that insulin accelerates Alzheimer-related pathology through its effects on the amyloid beta (A?) metabolism and tau phosphorylation.Asymptomatic ischemic lesions in T2DM subjects may lower the threshold for the development of dementia and this may explain the inconsistency between the basic research and clinicopathological studies.More research to elucidate the mechanism of neurodegeneration associated with T2DM is warranted.

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